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过表达的假基因通过调节促进肿瘤免疫浸润并提示乳腺癌预后较好。

Overexpressed Pseudogene Promotes Tumor Immune Infiltrates by Regulating and Indicates a Better Prognosis in Breast Cancer.

作者信息

Lyu Lijuan, Yao Jia, Wang Meng, Zheng Yi, Xu Peng, Wang Shuqian, Zhang Dai, Deng Yujiao, Wu Ying, Yang Si, Lyu Jun, Guan Feng, Dai Zhijun

机构信息

Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

出版信息

Front Oncol. 2020 Aug 7;10:1245. doi: 10.3389/fonc.2020.01245. eCollection 2020.

Abstract

Immune checkpoint inhibitors (ICIs) have been successfully used for treating melanoma and non-small cell lung cancer. However, many patients with breast cancer (BC) show low response to ICIs due to the paucity of infiltrating immune cells. Pseudogenes, as a particular kind of long-chain noncoding RNA, play vital roles in tumorigenesis, but their potential roles in tumor immunology remain unclear. In this study that used data from online databases, the novel pseudogene and its parental gene were overexpressed and correlated with better prognosis in BC. Mechanistically, our results revealed that might serve as an endogenous RNA to increase expression by competitively binding with . Functionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the axis was strongly relevant to immune-related biological functions. Further analysis demonstrated that high expression levels of the and were significantly associated with high immune infiltration abundance of CD8+ T cells, CD4+ T cells, Tfh, Th1, and NK cells and with high expression of majority biomarkers of monocytes, NK cell, T cell, CD8+ T cell, and Th1 in BC and its subtype, indicating that can increase the abundance of tumor-infiltrating lymphocytes in the BC microenvironment. Also, the and expression levels positively correlated with the expression levels of programmed cell death protein 1, programmed cell death ligand 1, and cytotoxic T-lymphocyte-associated antigen-4. Our findings suggest that pseudogene can upregulate through sponging has-miR-370-3p, thus exerting its antitumor effect by recruiting tumor-infiltrating immune cells into the breast tumor microenvironment, and that targeting the axis with ICIs may optimize the current immunotherapy for BC.

摘要

免疫检查点抑制剂(ICIs)已成功用于治疗黑色素瘤和非小细胞肺癌。然而,许多乳腺癌(BC)患者由于浸润免疫细胞稀少,对ICIs的反应较低。假基因作为一种特殊的长链非编码RNA,在肿瘤发生中起着至关重要的作用,但其在肿瘤免疫学中的潜在作用仍不清楚。在这项使用在线数据库数据的研究中,新型假基因及其亲本基因在BC中过表达且与较好的预后相关。机制上,我们的结果显示可能作为内源性RNA通过与竞争性结合来增加表达。功能上,基因本体(GO)和京都基因与基因组百科全书富集分析表明轴与免疫相关生物学功能密切相关。进一步分析表明,和的高表达水平与BC及其亚型中CD8 + T细胞、CD4 + T细胞、滤泡辅助性T细胞(Tfh)、Th1和自然杀伤细胞(NK细胞)的高免疫浸润丰度以及单核细胞、NK细胞、T细胞、CD8 + T细胞和Th1的大多数生物标志物的高表达显著相关,表明可增加BC微环境中肿瘤浸润淋巴细胞的丰度。此外,和的表达水平与程序性细胞死亡蛋白1、程序性细胞死亡配体1和细胞毒性T淋巴细胞相关抗原4的表达水平呈正相关。我们的研究结果表明,假基因可通过海绵吸附has - miR - 370 - 3p上调,从而通过将肿瘤浸润免疫细胞募集到乳腺肿瘤微环境中发挥其抗肿瘤作用,并且用ICIs靶向轴可能会优化当前BC的免疫治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e40e/7438735/2fee98e51ec7/fonc-10-01245-g0001.jpg

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